1-153975871-A-C

Position:

• chr1-153975871-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006694.4(JTB):​c.239T>G​(p.Val80Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: JTB NM_006694.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59

Genes affected

JTB (HGNC:6201): (jumping translocation breakpoint) Enables protein kinase binding activity. Involved in mitotic cytokinesis and positive regulation of protein kinase activity. Located in cytoplasm and midbody. Colocalizes with centrosome and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JTB	NM_006694.4	c.239T>G	p.Val80Gly	missense_variant	4/5	ENST00000271843.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JTB	ENST00000271843.9	c.239T>G	p.Val80Gly	missense_variant	4/5	1	NM_006694.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.239T>G (p.V80G) alteration is located in exon 4 (coding exon 4) of the JTB gene. This alteration results from a T to G substitution at nucleotide position 239, causing the valine (V) at amino acid position 80 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.64	T;.;.;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.2	M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.97	D;.;.;.
Vest4		0.46
MutPred		0.48		Gain of disorder (P = 0.0237);.;.;.;
MVP		0.61
MPC		1.7
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153948347;